The objective of the Specialized Cooperate Centers Program in Reproductive Research (SCCPRR) at the University of Illinois is to conduct innovative basic and clinical research in the reproductive sciences. Four projects are proposed Projects I (Project by Fazleabas) and II (Project by Bulun) focus on the etiology and pathophysiology of endometriosis while Projects II (Project by Gibori) and IV (Project by Nowak) address important questions relating to decidualization and implantation in rodent models, however, will be directly applicable to understanding the physiology and pathobiology of human reproduction. Project I "Endometriosis in the Baboon"-will test the hypothesis that the development of endometriosis occurs in two distinct phases. The data generated will determine if ovarian steroids are necessary to first establish to first establish the disease and if local steroid biosynthesis will maintain it. This project will also establish a direct link between endometriosis and aberrations in uterine receptivity. Project II "Hormone Action in Endometriosis"will test the hypothesis that progesterone resistance in endometriotic tissue disrupts the induction of the key estradiol (E2) metabolizing enzyme 17beta- hydroxydehydrogenase (HSD) type 2. A major goal is to determine whether aberrations in nuclear receptor expression causing progesterone resistance and the absence of 17beta-HSD-2 giving rise to increased tissue 32 levels are responsible for altered cell fate in endometriosis. Project III "Cell Signaling and Gene Regulation in Decidual Development" will focus on the functional role of decidual- derived proteins. Using transgenic mice mod3els, the role and regulation of cell cycle inhibitors, activin A and prolactin in the development and maintenance of the decidua during pregnancy will be evaluated. Project IV "EMMPRIN Regulates Metalloproteinases in the Endometrium" tests the hypothesis that an inducer of metalloproteinases (EMMPRIN) that is secreted by uterine epithelial cells regulates metalloproteinase (MMP) production in the endometrium. These studies will focus on the importance of MMPs in implantation and determine if EMMPRIN expression is required for MMP production by endometriotic tissue. These projects will be supported by an administrative core and two research cores: A) Imaging and Microscopy and B) Tissue Procurement and Cell Culture. These research cores will operate in an open access formula and support 7 other NIH approved grants whose research objectives will contribute but will not infringe upon the goals of the U54 application. The U54 Center at the University of Illinois will be established within a strong interactive and collegial environment and in an institution that has a rich history in reproductive research.